We propose to continue a wide-ranging program of research on the molecular bases of the nature and specificity of nucleic acid-protein interactions involved in the generation of physiologically-relevant genome control systems. We plan to complete our examination of the equilibrium and kinetic interactions of E. coli lac repressor with operator and non-operator DNA, which is designed to further elucidate the molecular mechanism of this part of the lac operon control system. In particular, we wish to understand how repressor (as well as other proteins which bind to double-stranded DNA) are translocated to their specific target sites. We also plan to continue studies on the kinetics and the equilibria of the interaction between DNA and helix-destablizing proteins (defined as proteins which bind preferentially to single-stranded nucleic acids and thus destabilize the double-helix). In particular, we are examining the equilibrium specificity and kinetics of the binding of T4-coded gene 32-protein to nucleic acids which can serve as models of the single-stranded DNA of the replication fork in DNA synthesis, and the specific mRNA involved in the autogeneous regulation of the synthesis of T4-coded gene 32-protein. The interaction of gene 32-protein with other components of the DNA replication system are also underway. In addition, we are continuing studies on the EcoRI restructuib-modification system, examining in particular the binding of these enzymes to double-stranded target sequences in solvent environments in which binding specificity is somewhat "relaxed", in order to learn more, about the interactions involved in specific recognition of target base pair sequences by genome regulatory proteins. The emphasis throughout these studies will continue to be on the elucidation of general principles required for a molecular understanding of genome regulatory systems in prokaryotes and eukaryotes.